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Gliomas originating in the neuroepithelium account for about 80% of brain malignancies and are the most common cancer of the central nervous system. Clinical management of gliomas remains challenging despite significant advances in comprehensive therapies, including radiotherapy, chemotherapy, and surgery. The ITGB4 (Integrin subunit beta 4) gene encodes a receptor for laminins and its upregulation in tumor tissues is associated with poor prognosis. However, its role in glioma is not well understood. First, we performed a pan cancer analysis of ITGB4 expression in The Cancer Genome Atlas (TCGA) dataset. Survival analysis was done on Chinese Glioma Genome Atlas (CGGA) and TCGA. Immunohistochemistry was then used to validate the expression and role of ITGB4 in glioma. We finally analyzed the possible mechanism by immune infiltration and single-cell sequencing analysis. Here, we found that ITGB4 is upregulated in glioma and accurately predicts the prognosis of lower grade glioma (LGG). Univariate and multivariate Cox regression analyses showed that ITGB4 is a risk factor for LGG. Immunohistochemical analysis confirmed that ITGB4 accurately predicts LGG prognosis. Non-negative matrix factorization (NMF) cluster analysis showed that ITGB4 was closely related to immune related genes. Immune cell infiltration and single cell sequencing analyses indicated that ITGB4 may be closely related to the microenvironment of gliomas, especially tumor-associated fibroblasts. ITGB4 is a promising diagnostic and therapeutic factor in LGG patients. [ABSTRACT FROM AUTHOR]

Garnet amphibolite is one of the common metabasic rocks exposed in collisional orogenic belt, the metamorphic evolution of which is associated closely with orogenic processes. The Yaganbuyang garnet amphibolites occur as blocks hosted by massive granitic gneiss, and consist mainly of hornblende, garnet, clinopyroxene, plagioclase, biotite, quartz with minor rutile/ilmenite and phengitic muscovite. These garnet amphibolites were interpreted to have experienced decompression-dominated evolution that can be divided into three generations (M1, M2, M3), based on the petrographic observations and phase equilibria modeling calculated by THERMOCALC. The assemblage of the first generation (M1) is inferred to possibly be dominated by garnet + omphacite + rutile + phengite + quartz, which is modeled to be roughly stable at P > 25 kbar and T > 800 °C. The second generation (M2) is characterized by the local symplectites of clinopyroxene + plagioclase produced from omphacite, indicating a near-isothermal decompression from ∼23.8 kbar/875 °C to ∼10 kbar/852 °C. The third generation (M3) is marked by the kelyphitic rims of plagioclase + hornblende around garnet and of hornblende + ilmenite around clinopyroxene, involving the late-stage retrogression from ∼9.8 kbar/848 °C to ∼5.8 kbar/645 °C. Zircon U-Pb dating yielded one group metamorphic age of c. 500 Ma that is interpreted to represent the timing of the peak eclogite-facies metamorphism. A combination of petrography observation, phase modeling results and geochronology data suggests that the Yaganbuyang garnet amphibolites have once undergone eclogite-facies metamorphism by continental subduction rather than crustal thickening. Therefore, the Yaganbuyang area is an eastward extension part of the South Altyn HP-UHP metamorphic belt. [ABSTRACT FROM AUTHOR]

Discontinuous dewetting is an attractive technique that can produce droplet array of specific volume, geometry and at predefined location on a substrate. Droplet array has great potential in bioanalysis such as high-throughput live cell screening, digital PCR, and drug candidates. Here, we propose a self-dispersing droplet array generation method, which has advantages of low cost, simple operation, and easy large-area production ability. Droplet array of specific volumes was generated on a polymethyl methacrylate (PMMA) substrate using a simple reusable polyimide (PI) adhesive mask. Experiment shows that the generated droplet array can be used to successfully capture single particles which obeys Poisson distribution in a high-throughput manner. Furthermore, a droplet-array sandwiching chip was created based on the self-dispersion method for rapid detection of human serum albumin (HSA) at wide range of 183–11,712 μg/mL with low reagent consumption of 2.2 μL, demonstrating its potential applications in convenient high-throughput bioanalysis and bioassays. [ABSTRACT FROM AUTHOR]

Summary: Chemotherapy has always been the first therapeutic option for patients with advanced non-small cell lung cancer (NSCLC) with untreatable oncogenic mutations. However, chemotherapy has demonstrated limited success and is associated with severe side effects. This research aimed to investigate the antitumor efficacy and cytotoxic safety of the conjugate ZHER2:V2-pemetrexed, a novel targeted chemotherapeutic drug. In this context, human epidermal growth factor receptor 2 (HER2) + A549 lung xenografts were treated using ZHER2:V2-pemetrexed, pemetrexed or physiological saline. Therapeutic efficacy was monitored by single photon emission computed tomography (SPECT) imaging using the 99mTc-labeled ZHER2:V2-pemetrexed conjugate and further confirmed by performing apoptosis assays using flow cytometry analysis and hematoxylin-eosin (H&E) staining. To evaluate the expression of HER2 in tumor tissues, immunohistochemistry was performed, accompanied by quantitative analysis using flow cytometry. A toxicological evaluation was also conducted. Imaging with 99mTc-ZHER2:V2-pemetrexed demonstrated that in HER2+ A549 models, ZHER2:V2-pemetrexed showed better antineoplastic effects than pemetrexed. Compared with pemetrexed, the results from the pathological and flow cytometry analyses also revealed that ZHER2:V2-pemetrexed exhibits high antitumor activity against A549 tumors, inducing necrosis, apoptosis and cell cycle arrest. In addition, the clinical signs of toxicity in the ZHER2:V2-pemetrexed treated group were reduced compared with those in the pemetrexed treated group. These data revealed that the ZHER2:V2-pemetrexed conjugate encompasses promising targeted antitumor activity against HER2-positive lung adenocarcinoma, with reduced side effects compared with pemetrexed. Thus, the ZHER2:V2-pemetrexed conjugate may serve as a novel molecular agent with tremendous clinical breakthrough potential in the diagnosis and treatment of HER2-positive lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Mafic dyke swarm is widely developed in Proterozoic continental lithosphere. The Gangou diabase dyke from the Xixia area, intruded into the Douling complex of the South Qinling belt, yields zircon UPb age of 731 Ma. It has low SiO2 content (49.02 wt.%-49.37 wt.%) and Mg# (34.0–37.7) and shows characteristics of subalkaline tholeiite series. They show high ΣREE (155.5×10 6–184.7×106), weak negative Eu anomaly (SEu=0.88-0.93), slight depletion of Nb and Ta, and enrichment of LILE. Their major and trace element, Sr-Nd-Pb isotope and clinopyroxene compositions indicate that it originated from the partial melting of the asthenospheric mantle within-plate extension setting and was slightly contaminated by crust compositions. The similarities of formation age, petrogenesis, source characteristic and tectonic setting for Gangou diabase with mafic dykes in Wudang Block and mafic volcanic rocks in Yaolinghe Group indicate that the South Qinling belt underwent strong continental extension in Neoproterozoic during 796–685 Ma most likely correspondence to the breaking-up of the Rodinia supercontinent. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. In the present study, the function of amyloid precursor protein (APP) in modulating capacitive calcium entry (CCE), a refilling mechanism for depleted intracellular calcium stores, was investigated. CCE in neural 2a (N2a) cells stably expressing wild-type human APP was lower than in wild-type N2a cells, while CCE in APP knockout mouse embryonic fibroblast (MEF) cells was higher than in their wild-type counterparts. We demonstrate that wild-type APP depresses CCE. Furthermore, using N2a cells transfected with C-terminal APP fragments, we show that these fragments anchored in the cell membrane play an important role in CCE depression. [ABSTRACT FROM AUTHOR]